Hydrate dehydration mechanism

Fig. 5-20. Proposal for the hydration-dehydration mechanism of carbonic anhydrase. The pK of the zinc bound water is envisaged to be lowered to about 7.0 by the charge distribution on the metal ion and also helped by Glu-196 by the hydrogen bonding through Thr-199.

Neither the AdE3 nor the AdE2 mechanism is consistent with available data concerning the acid catalyzed hydration of propene to 2-propanol in supercritical water at 375 C and 34.5 MPa. More data are being accumulated to sustain a rigorous kinetic examination of the hydration/dehydration mechanism. 

Yang, X. et al.. Surface acid-base properties and hydration/dehydration mechanisms of aluminum (hydr)oxides, J. Colloid Interf. Sci., 308. 395, 2007. 

The molecular mechanism of enzymatic isomerization is far from being fully understood. In a study of Pseudomonas sp. strain E-3 the similarity between cis-trans isomerase and LOX was hypothesized on the basis of the common inhibition given by antioxidants. However, chelating agents, which do not affect isomerization, also inhibit LOX. A second mechanistic hypothesis was then formulated, consisting of the hydration-dehydration mechanism, similar to the formation of 3-trans-enoyl-CoA from the corresponding cis isomer [28]. Another recent mechanism was proposed based on analysis of carbon isotope fractionation of CTI [25]. Scheme 6.3 shows the proposed mechanism of CTI based on the enzyme-substrate complex as an intermediate, which allows the rotation of the carbon-carbon double bond to occur. 

Reaction Mechanism and Kinetics. The equiHbria involved ia the hydration—dehydration of ethylene first proposed (117) can be expressed as follows ... 

Cu(II) complexes have been synthesized and stndied to mimic the catalytic activity of CA24 247 Mechanistic stndies have assisted to reveal the details of the hydration and dehydration mechanism and the catalytic activity of the model complexes 51... 

The catalytic mechanism for C02 hydration-dehydration by carbonic anhydrase represents the focal issue of the present discussion. We have to consider two aspects (1) the mode of binding of the C02 substrate at the active site, and (2) the physical-chemical state of ligands on the zinc ion. 

Acetazolamide is a carbonic anhydrase (CAH) inhibitor that acts predominantly in the proximal convoluted tubules. Its mechanism of action can be summarized as follows. Reabsorption of Na+ is decreased because fewer H+ ions are available for the Na+/H+ antiporter. As a result, excretion of Na+ and H20 increases. CAH accelerates attainment of equilibrium of C02 hydration/dehydration reactions ... 

Figures 2a and 2b display the acid catalyzed E2 and El mechanisms for the dehydration of 1-propanol and 2-propanol. Note that the El mechanism involves four more rate constants (kinetic parameters) than the related E2 dehydration mechanism. Chemists employ the terminology (1) Adg3 to describe the hydration mechanism which forms 2-propanol from propene in Figure 2a, and Ad 2 to refer to the mechanism which forms 2-propanol from propene in Figure 2b. In this paper we do not distinguish between bare carbocations, Il-complexes, encumbered carbocations and symmetrically solvated carbocations, since these intermediates all manifest themselves similarly in the El kinetic model.

The ambient concentration of CO2 in seawater ( 10 pM) is low compared to the half saturation constant of RubisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) the enzyme that fixes the inorganic carbon into PG3 (3-phos-phoglycerate) in the first step of the Calvin cycle (the dark reaction of photosynthesis). Microalgae have thus evolved various carbon concentrating mechanisms (CCM) to augment the CO2 concentration at the site of fixation [55]. These mechanisms all involve interconversion between CO2 and HCOJ at some point. But at neutral pH the hydration/dehydration reaction of CO2/ HCOj" has a half life of 30 s, much too slow for a cellular process (for example, diffusion from one end of the cell to the other takes on the order of 10 ms), and requires catalysis. The enzyme CA is an extraordinary effective catalyst some CA catalyze the CO2/HCO3 reaction at a rate that nearly reaches the limit imposed by the diffusion of molecules [56]. 

This hydration-dehydration equilibrium illustrates a very important principle in the study of reaction mechanisms—the principle of microscopic reversibility. According to this principle, the sequence of transition states and reactive intermediates (i.e., the mechanism) for any reversible reaction must be the same, but in reverse order, for the reverse reaction as for the forward reaction. 

But we can assign to GSH more specific functions also. It participates in transpeptidations and oxidation reductions as well as in hydration-dehydration reactions. Perhaps this large variety of reactions has more in common than appears at first sight. Many of the transpeptidation reactions have been shown to occur with enzymes such as the cathepsins which require SH groups for activity. Hydrolysis of thiol esters by papain has been recently demonstrated (66) and the formation of thiol esters as intermediates in transpeptidations still remains to be explored. In the glyoxalase reaction the actual substrate may be the hydrated form of the aldehyde, in which case the reaction mechanism would be one of dehydration and hydrolysis rather than of a hydrogen shift. Thus the reaction will bear some similarity to the aconitase reaction which is stimulated by SH compounds and ferrous ions (67). 

The insertion of CO2 into discrete covalent polar M-OH bonds has long been investigated because as the reaction is related to the conversion of CO2 into its hydrated forms (anionic or coordinated HCOs" and the elusive acid H2CO3 which cannot be isolated as a pure compound), a reaction that plays a key role in CO2 elimination in humans and animals in the respiratory process. Such a reaction is relevant to the enzyme carbonic anhydrase (CA) which accelerates the reaction of hydration-dehydration of CO2, thus facilitating its uptake at the cellular level and its elimination in the lungs from where it is expelled [30]. Scheme 4.7 shows the mechanism of reaction of CO2 with the Zn-OH moiety, active center of CA. 

Figure 13. Exaggerated free energy surface showing two volcanoes with contours for a concerted proton transfer. At all values of the C-O distance there is a barrier to proton transfer. The Marcus theory of proton transfer predicts that a = since the saddle occurs at the value of x where the thermodynamics driving the proton transfer is in balance (QRS). The surface has been drawn for a symmetrical case, but this conclusion still holds for an unsymmetrical case. The strip cartoon shows the mechanism for the hydration dehydration reaction of a ketone.

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